Reovirus Plus Radiation Act Synergistically Against Cancer

Newswise — Since the advent of cancer therapy, clinicians and patients have sought more targeted treatments that attacked tumors while sparing normal tissues. Several viruses, including the reovirus, or Respiratory Enteric Orphan virus, have shown a strong preference for killing cancer cells vs. normal cells. These oncolytic (tumor-bursting) viruses represent an entirely new approach to cancer treatment.

Calgary-based Oncolytics Biotech has recently reported encouraging results from a U.K. Phase Ia/Ib clinical trial with its Reolysin® oncolytic reovirus formulation in combination with radiation for patients with a variety of advanced or metastatic cancers. The rationale for the trial emerged after preclinical work demonstrated that the addition of radiation enhanced the cancer-killing ability of Reolysin. Interim results from the Phase Ia/b human study suggest this is true.

Oncolytics Biotech reported these findings at the International Conference on Molecular Targets and Cancer Therapeutics in San Francisco in late October, 2007, where Dr. Dean Harris of London's Institute of Cancer Research presented the results. The data are available on the Oncolytics website at: http://media.integratir.com/T.ONC/ppt/Reo_Rtx_Poster_aacr_2007_final.pdf

The study has treated 22 middle-aged and elderly patients with various tumor types to date. Patients were split into two groups that received either 20 or 36 Gy of radiation, along with escalating dosages of two to six injections of REOLYSIN into a target tumour. Tumors included melanomas and cancers of the colon, pancreas, ovaries, larynx, and other sites. No serious or dose-limiting side effects were noted.

Although this safety study was not designed to show tumor shrinkage, investigators noted a positive trend towards efficacy. Of the 11 patients in the Ia study, three experienced significant partial responses. Three of the 6 patients who completed the Ib trial also responded to treatment. Typically, only 5% to 15% of patients with advanced cancer respond to conventional cancer treatments. These particular patients had cancers that either did not respond to cancer treatment, or for whom no other treatments were available.

Dr. Brad Thompson, President and CEO of Oncolytics, is encouraged by the results. "The study demonstrates that Reolysin plus radiation is quite safe at the levels administered," he said. "We are also hopeful about the anti-tumor activity data from the Phase Ia/b trials," he added. "These patients were very sick. Any improvement in their condition is cause for optimism."

What was particularly noteworthy in this trial was that patients experienced tumor responses both at the injection site and also in non-injected tumors. Oncolytics has noted this effect in earlier studies as well. This may have been caused by the reovirus traveling through the bloodstream to other tumors. It could also have been caused by an immune response which fights tumors that have not been directly infected by reovirus. This "bystander effect" , caused by the priming of the immune system from the initial tumor killing by reovirus, can endure for weeks or months after treatment.

Reovirus is a double-stranded RNA virus that causes asymptomatic human infection. When it encounters cancer cells, reovirus invades and produces thousands of copies of itself, causing the cell to burst. The reovirus selectivity is based on its ability to exploit a pathway specific to cancer cells. Specifically, reovirus only infects cells that possess ras, an activated cancer signaling pathway that operates in about 70% of human cancers. Ras acts as a kind of switch to allow reovirus to invade and destroy the cell. Normal cells keep ras (the name of both a gene and its protein product) in check; cancer cells lose control over Ras, resulting in the uncontrolled growth characteristic of deadly tumors.

The Ib phase of this trial is almost complete. Oncolytics is also enrolling patients in a Phase II trial for this treatment combination. In addition, the company is testing Reolysin, alone and in combination with radiation or chemotherapy, in Phase I and Phase II human trials for several cancer types.

For more information, log on to http://www.oncolyticsbiotech.com